RESEARCH ON CRYSTAL DEPOSITION ARTHROPATHIES
RELEASE DATE: December 5, 2003
RFA Number: RFA-AR-04-006
Department of Health and Human Services (DHHS)
PARTICIPATING ORGANIZATION:
National Institutes of Health (NIH)
(http://www.nih.gov)
COMPONENTS OF PARTICIPATING ORGANIZATION:
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
(http://www.nih.gov/niams/)
National Institute on Aging (NIA)
(http://www.nih.gov/nia/)
CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER: 93.846 (NIAMS) and 93.866 (NIA)
LETTER OF INTENT RECEIPT DATE: July 19, 2004
APPLICATION RECEIPT DATE: August 19, 2004
THIS RFA CONTAINS THE FOLLOWING INFORMATION
o Purpose of this RFA
o Research Objectives
o Mechanism(s) of Support
o Funds Available
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Where to Send Inquiries
o Letter of Intent
o Submitting an Application
o Peer Review Process
o Review Criteria
o Receipt and Review Schedule
o Award Criteria
o Required Federal Citations
PURPOSE OF THIS RFA
The National Institute of Arthritis and Musculoskeletal and Skin
Diseases (NIAMS) and the National Institute on Aging (NIA) invite
applications for research on improved diagnosis and treatment of the
major crystal deposition arthropathies including gout, calcium
pyrophosphate dihydrate (CPPD) crystal deposition disease and
hydroxyapatite crystal deposition disease (also known as basic calcium
phosphate crystallopathy). The applications may be for individual
research projects (R01) or for exploratory/developmental grants (R21).
The crystal deposition arthropathies constitute significant public
health problems. These problems are anticipated to grow in scope in
view of the increased number of elderly in our population, and the
increasing numbers of people with osteoarthritis predisposing cartilage
to calcification disorders. The Request for Applications (RFA) is
based, in part, on the scientific opportunities identified in the NIAMS
Roundtable held in 2003: "Opportunities for Translational Research on
Articular Crystal Deposition Diseases: Gout, CPPD Crystal Deposition
Disease, Hydroxyapatite Deposition Arthropathy."
RESEARCH OBJECTIVES
Gout is caused by the deposition of uric acid (monosodium urate)
crystals in connective tissue and in the joint space. Clinical
manifestations include bouts of gouty arthritis, tophaceous deposits,
uric acid and calcium oxalate kidney stones, and, rarely, interstitial
nephropathy. In some cases, uric acid crystals in the joints trigger
severe destruction of articular cartilage, leading to pain and
disability.
Uric acid is the normal end product of purine metabolism in humans. It
is generated as a result of nucleotide turnover and breakdown of
dietary purines, and its elimination is controlled primarily by the
kidneys. Because the human uric acid oxidase (uricase) gene contains a
mutation that renders it transcriptionally silent, normal serum levels
of uric acid are very close to the level at which urate becomes
insoluble in vitro, rendering urate balance precarious. Although
elevated serum uric acid levels are the first sign of gout, only about
20% of people with hyperuricemia develop the disease.
Gout affects approximately 1% of the U.S. population, and remains a
significant public health concern. The prevalence of gout is much
higher in certain ethnic groups, including Asian Pacific Islanders,
Filipinos, Maoris, and Samoans. Gout prevalence is also reportedly
rising in African Americans. Although gout primarily affects men,
disease prevalence is increasing among elderly women along with
increased longevity, and may be linked to the common use of diuretics
and chronic renal insufficiency in this population. Reduced estrogen
levels in postmenopausal women may also play a role, as estrogen is a
uricosuric agent.
Refractory gout still exists, and the numbers of affected patients may,
in fact, be increasing. This could be due to the limited scope of
currently available urate-lowering drugs and the relatively common and
potentially life-threatening toxicity of the most versatile uric acid–
lowering drug, allopurinol, which blocks urate production by inhibiting
xanthine oxidase. Another contributing factor is the increasing number
of people receiving kidney and heart transplants and the use of
cyclosporine to prevent tissue rejection in these patients. More than
10% of transplant patients develop gout within 3 years of treatment
with cyclosporine, and the rapidly expanding tophi and severe attacks
of gouty arthritis that occur in these patients are often refractory to
therapy.
The development of new treatments for gout has not kept pace with
medical needs. An estimated 10–20% of gout cases in the U.S. are
refractory to treatment because patients either cannot take allopurinol
or are resistant to the drug. In addition, the effectiveness of
uricosuric drugs such as probenecid is limited by various factors. The
principal therapies for acute gout attacks, i.e., nonsteroidal anti-
inflammatory drugs (including COX-2 inhibitors), glucocorticoids, and
colchicine, also have limitations and cannot prevent the progressive
crystal-induced connective tissue destruction that occurs in some gout
patients.
Non-urate calcium-containing crystal deposition diseases that affect
the joints and surrounding structures include calcium pyrophosphate
dihydrate (CPPD) crystal deposition disease and hydroxyapatite crystal
deposition disease (also known as basic calcium phosphate
crystallopathy). Some individuals have a mixture of CPPD and
hydroxyapatite crystals in affected joints. The prevalence and
incidence of calcium crystal arthropathies are expected to increase as
a result of the growing elderly population in the U.S. and increasing
numbers of people with osteoarthritis predisposing cartilage to
calcification disorders.
Manifestations of CPPD disease may include intermittent attacks of
pseudogout (acute inflammatory arthritis), chronic degenerative
arthropathy, and calcification of articular cartilage. CPPD disease
can occur idiopathically, and in rare cases as a hereditary condition.
Crystal deposition may be associated with a variety of metabolic
disorders and can also occur as a result of trauma, injury or surgery.
The basic calcium phosphate arthropathies include calcific
periarthritis syndromes that can occur as primary or secondary disease
manifestations and may occur in a familial fashion, in calcific
tendonitis and bursitis, intraarticular arthropathies such as Milwaukee
shoulder syndrome, and periarthropathies. Tumoral calcinosis syndrome
is a rare form of basic calcium phosphate marked by large,
periarticular tophaceous deposits containing hydroxyapatite and other
basic calcium phosphate crystals.
CPPD or hydroxyapatite crystals are present in synovial fluid extracted
from the joints of 30-60% of people with osteoarthritis, however, a
distinct pattern of joint involvement distinguishes CPPD and
hydryoxyapatite deposition diseases from "garden variety"
osteoarthritis. Definitive diagnosis of the calcium crystal deposition
arthropathies is made by identifying specific crystal types in synovial
fluid samples, which can be technically difficult. Chondrocalcinosis
and other soft tissue calcification may also be visible on X rays of
joints in some patients, although these patients may be asymptomatic.
CPPD and hydroxyapatite crystals may also contribute directly or
indirectly to osteoarthritis (OA). However, the mechanisms involved
are still unclear, and there is controversy as to whether crystals can
actually cause OA in some cases rather than just exacerbating the
disease.
In addition to studies of possible direct and indirect effects of
crystals on OA, ongoing research on calcium crystal arthropathies
includes studies of factors involved in cartilage mineralization,
investigations using animal models of articular calcification, and
genetic studies of familial disorders of calcium crystal deposition.
Recent advances include the identification of two molecules that play a
key role in some forms of CPPD and hydroxyapatite deposition diseases:
the pyrophosphate-generating ectoenzyme PC-1 (a nucleoside triphosphate
pyrophosphohydrolase) and ANKH, a multiple-pass transmembrane protein
expressed in articular cartilage and other tissues that is a putative
pyrophosphate transporter. Inorganic pyrophosphate is both a potent
inhibitor of hydroxyapatite deposition and an essential component of
CPPD crystals, indicating that it plays a central role in calcium
crystal deposition diseases.
This RFA is intended to stimulate research aimed at elucidating the
pathogenesis of these disorders and engender the development of
improved methods of diagnosis and treatment. Topics of interest
include but are not limited to:
Gout:
o Improving understanding of the fundamental pathobiology of gout,
including formation of tophi and the relationship between crystals and
pathology in arthritis
o Addressing the problem of treatment failure
o Determining why uric acid crystal deposition occurs in only some
people with hyperuricemia, with the goal of developing approaches that
prevent crystal formation in susceptible individuals
o Developing new methods for early diagnosis
o Conducting small-scale epidemiologic studies on gout
o Studying the genetic basis of drug responsiveness and drug resistance
o Developing new therapeutic agents
o Developing new animal models
Calcium Crystal Arthropathies:
o Improving understanding of the relationship between calcium crystals
and pathology
o Improving understanding of the basic biology of the link between
aging tissue changes and development of calcium crystal deposition
diseases
o Clarifying the relationship between calcium crystal deposition and
osteoarthritis
o Determining why some people with OA develop CPPD crystals in their
joints, some develop hydroxyapatite crystals, and some develop both
o Developing methods for early diagnosis of disease using biomarkers
and imaging modalities
o Identifying of risk factors for disease
o Developing new treatments, including ways to alleviate problems in
patients who already have crystal deposits as well as ways to prevent
crystal formation in specific joints, such as the knee, hip, shoulder,
temporomandibular joint, etc.
o Developing new animal models
Please note that large-scale clinical and epidemiologic studies are
beyond the scope of this RFA.
MECHANISMS OF SUPPORT
This RFA will use the NIH R01 (investigator-initiated research project
grant) and the R21 (exploratory/developmental research grant) award
mechanisms. As an applicant you will be solely responsible for
planning, directing, and executing the proposed project. This RFA is a
one-time solicitation. Future unsolicited, competing-continuation
applications based on this project will compete with all investigator-
initiated applications and will be reviewed according to the customary
peer review procedures. The anticipated award date is June 1, 2005.
Applications that are not funded in the competition described in this
RFA may be resubmitted as NEW investigator-initiated applications using
the standard receipt dates for NEW applications described in the
instructions to the PHS 398 application.
R01 Applications. Because the nature and scope of the research
proposed in response to this RFA may vary, it is anticipated that the
size of an award will vary also. This RFA uses just-in-time concepts.
It also uses the modular as well as the non-modular budgeting formats
(see http://grants.nih.gov/grants/funding/modular/modular.htm).
Specifically, if you are submitting an application with direct costs in
each year of $250,000 or less, use the modular format. Otherwise
follow the instructions for non-modular research grant applications.
This program does not require cost sharing as defined in the current
NIH Grants Policy Statement at
http://grants.nih.gov/archive/grants/policy/nihgps_2001/part_i_1.htm.
R21 Applications. This mechanism is to be used by investigators
experienced in arthritis and musculoskeletal diseases research who wish
to conduct innovative, high-risk studies. Also encouraged to apply are
investigators with expertise in fields other than arthritis and
musculoskeletal diseases that wish to establish new research programs
on these diseases.
Exploratory/developmental studies are not intended for large-scale
undertakings or to support or supplement ongoing research. Instead,
investigators are encouraged to explore the feasibility of an
innovative research question or approach which may not be justifiable
through existing research to compete as a standard research project
grant (e.g., R01), and to develop a research basis for a subsequent
application through other mechanisms, i.e., R01, P01.
Exploratory/developmental (R21) grants may not exceed $100,000 per year
in direct costs. The total project period for an R21 application
submitted in response to this RFA may not exceed two years. These
grants are non-renewable and continuation of projects developed under
the R21 program will be through the traditional unsolicited (R01 or
P01) grant programs.
This RFA uses just-in-time concepts. It also used the modular
budgeting as well as the non-modular budgeting formats (see
http://grants.nih.gov/grants/funding/modular/modular.htm).
Specifically, if you are submitting an application with direct costs in
each year of $250,000 or less, use the modular budget format.
Otherwise follow the instructions for non-modular budget research grant
applications. This program does not require cost sharing as defined in
the current NIH Grants Policy Statement at
http://grants.nih.gov/grants/policy/nihgps2001/part_i_1.htm.
Investigators proposing to conduct small, pilot/toxicity clinical
trials are advised to review the NIAMS guidelines for preparation of
clinical trial applications and the NIAMS guidelines for Data and
Safety Monitoring Boards (http://www.nih.gov/niams.htm).
FUNDS AVAILABLE
The estimated funds available for the first year of support for the
program are $1,200,000 in FY 2005 to fund 3 to 5 new grants in response
to this RFA. Because the nature and scope of the proposed research
will vary from application to application, it is anticipated that the
size and duration of each award will also vary. Although the financial
plans of the NIAMS provide support for this program, awards pursuant to
this RFA are contingent upon the availability of funds and the receipt
of a sufficient number of meritorious applications. At this time, it is
not known if this RFA will be reissued.
ELIGIBLE INSTITUTIONS
You may submit (an) application(s) if your institution has any of the
following characteristics:
o For-profit or non-profit organizations
o Public or private institutions, such as universities, colleges,
hospitals, and laboratories
o Units of State and local governments
o Eligible agencies of the Federal government
o Domestic or foreign institutions/organizations
o Faith-based or community-based organizations
INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS
Any individual with the skills, knowledge, and resources necessary to
carry out the proposed research is invited to work with their
institution to develop an application for support. Individuals from
underrepresented racial and ethnic groups as well as individuals with
disabilities are always encouraged to apply for NIH programs.
WHERE TO SEND INQUIRIES
We encourage inquiries concerning this RFA and welcome the opportunity
to answer questions from potential applicants. Inquiries may fall into
three areas: scientific/research, peer review, and financial or grants
management issues:
o Direct your questions about scientific/research issues to:
Bernadette Tyree, Ph.D.
Director, Cartilage and Connective Tissue Program
NIAMS
One Democracy Plaza
6701 Democracy Boulevard, Suite 800, MSC 4872
Bethesda, MD 20892-4872
Telephone: (301) 594-5032
FAX: (301) 480-1284
Email: tyreeb@mail.nih.gov
Jill L. Carrington, Ph.D.
Director, Musculoskeletal Biology
Biology of Aging Program
National Institute on Aging
7201 Wisconsin Avenue, Suite 2C231
Bethesda, MD 20892
Telephone: (301) 496-6402
FAX: (301) 402-0010
Email: Carringtonj@nia.nih.gov
o Direct your questions about peer review issues to:
Teresa Nesbitt, D.V.M., Ph.D.
Chief, Review Branch
NIAMS
One Democracy Plaza
6701 Democracy Boulevard, Suite 800, MSC 4872
Bethesda, MD 20892-4872
Telephone: (301) 594-4953
FAX: (301) 480-4543
Email: nesbittt@mail.nih.gov
o Direct your questions about financial or grants management matters
to:
Michael Morse
Grants Management Branch
NIAMS
One Democracy Plaza
6701 Democracy Boulevard, Suite 800, MSC 4872
Bethesda, MD 20892-4872
Telephone: (301) 594-3535
FAX: (301) 480-5450
Email: morsem@mail.nih.gov
Linda Whipp
Grants and Contracts Management Office
National Institute on Aging
7201 Wisconsin Avenue, Suite 2N212, MSC 9205
Bethesda, MD 20892
Telephone: (301) 496-1472
FAX: (301) 402-1758
Email: whippl@nih.nih.gov
LETTER OF INTENT
Prospective applicants are asked to submit a letter of intent that
includes the following information:
o Descriptive title of the proposed research
o Name, address, and telephone number of the Principal Investigator
o Names of other key personnel
o Participating institutions
o Number and title of this RFA
Although a letter of intent is not required, is not binding, and does
not enter into the review of a subsequent application, the information
that it contains allows NIAMS staff to estimate the potential review
workload and plan the review.
The letter of intent is to be sent by the date listed at the beginning
of this document. The letter of intent should be sent to:
Teresa Nesbitt, D.V.M., Ph.D.
Chief, Review Branch
NIAMS
One Democracy Plaza
6701 Democracy Boulevard, Suite 800, MSC 4872
Bethesda, MD 20892-4872
Telephone: (301) 594-4953
FAX: (301) 480-4543
Email: nesbittt@mail.nih.gov
SUBMITTING AN APPLICATION
Applications must be prepared using the PHS 398 research grant
application instructions and forms (rev. 5/2001). Applications must
have a DUN and Bradstreet (D&B) Data Universal Numbering System (DUNS)
number as the Universal Identifier when applying for Federal grants or
cooperative agreements. The DUNS number can be obtained by calling
(866) 705-5711 or through the web site at
http://www.dunandbradstreet.com/. The DUNS number should be entered on
line 11 of the face page of the PHS 398 form. The PHS 398 document is
available at http://grants.nih.gov/grants/funding/phs398/phs398.html in
an interactive format. For further assistance contact GrantsInfo,
Telephone (301) 435-0714, Email: GrantsInfo@nih.gov.
SUPPLEMENTARY INSTRUCTIONS
RESEARCH PLAN – The research plan (a-d) is limited to 25 pages for R01
applications and 10 pages for R21 applications. Applications that
exceed the page limit will be returned without review. An appendix may
be included in the application; however, the appendix is not to be used
to circumvent the page limit of the research plan.
For the R21 application, preliminary data supporting feasibility of
approach are not required, however, if included, the section may not
exceed 1 page. In addition, a paragraph should be included in the
Significance section of the application that specifies either how the
project presents a new direction for the work performed in the PI's
laboratory or the innovative nature of the research question or
approach, and how it may advance understanding of the crystal
deposition arthropathies.
SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS: Applications
requesting up to $250,000 per year in direct costs must be submitted in
a modular grant format. The modular grant format simplifies the
preparation of the budget in these applications by limiting the level
of budgetary detail. Applicants request direct costs in $25,000
modules. Section C of the research grant application instructions for
the PHS 398 (rev. 5/2001) at
http://grants.nih.gov/grants/funding/phs398/phs398.html includes step-
by-step guidance for preparing modular grants. Additional information
on modular grants is available at
http://grants.nih.gov/grants/funding/modular/modular.htm.
USING THE RFA LABEL: The RFA label available in the PHS 398 (rev.
5/2001) application form must be affixed to the bottom of the face page
of the application. Type the RFA number on the label. Failure to use
this label could result in delayed processing of the application such
that it may not reach the review committee in time for review. In
addition, the RFA title and number must be typed on line 2 of the face
page of the application form and the YES box must be marked. The RFA
label is also available at:
http://grants.nih.gov/grants/funding/phs398/labels.pdf.
SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten
original of the application, including the Checklist, and three signed,
photocopies, in one package to:
Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD 20892-7710
Bethesda, MD 20817 (for express/courier service)
At the time of submission, two additional copies of the application
must be sent to:
Teresa Nesbitt, D.V.M., Ph.D.
Chief, Review Branch
NIAMS
One Democracy Plaza
6701 Democracy Boulevard, Suite 800, MSC 4872
Bethesda, MD 20892-4872
Telephone: (301) 594-4953
FAX: (301) 480-4543
Email: nesbittt@mail.nih.gov
APPLICATION PROCESSING: Applications must be received on or before the
application receipt date listed in the heading of this RFA. If an
application is received after that date, it will be returned to the
applicant without review.
Although there is no immediate acknowledgement of the receipt of an
application, applicants are generally notified of the review and
funding assignment within 8 weeks.
The Center for Scientific Review (CSR) will not accept any application
in response to this RFA that is essentially the same as one currently
pending initial review, unless the applicant withdraws the pending
application. However, when a previously unfunded application,
originally submitted as an investigator-initiated application, is to be
submitted in response to an RFA, it is to be prepared as a NEW
application. That is, the application for the RFA must not include an
Introduction describing the changes and improvements made, and the text
must not be marked to indicate the changes from the previous unfounded
version of the application.
PEER REVIEW PROCESS
Upon receipt, applications will be reviewed for completeness by the CSR
and responsiveness by the NIAMS and the NIA. Incomplete applications
will not be reviewed.
Applications that are complete and responsive to the RFA will be
evaluated for scientific and technical merit by an appropriate peer
review group convened by the NIAMS in accordance with the review
criteria stated below. As part of the initial merit review, all
applications will:
o Undergo a process in which only those applications deemed to have the
highest scientific merit, generally the top half of the applications
under review, will be discussed and assigned a priority score
o Receive a written critique
o Receive a second level review by an appropriate national advisory
council or board.
REVIEW CRITERIA
The goals of NIH-supported research are to advance our understanding of
biological systems, improve the control of disease, and enhance health.
In the written comments, reviewers will be asked to evaluate the
application in order to judge the likelihood that the proposed research
will have a substantial impact on the pursuit of these goals. The
scientific review group will address and consider each of the following
criteria in assigning the application's overall score, weighting them
as appropriate for each application.
o Significance
o Approach
o Innovation
o Investigator
o Environment
The application does not need to be strong in all categories to be
judged likely to have major scientific impact and thus deserve a high
priority score. For example, an investigator may propose to carry out
important work that by its nature is not innovative but is essential to
move a field forward.
SIGNIFICANCE: Does this study address an important problem? If the aims
of the application are achieved, how will scientific knowledge be
advanced? What will be the effect of these studies on the concepts or
methods that drive this field?
APPROACH: Are the conceptual framework, design, methods, and analyses
adequately developed, well integrated, and appropriate to the aims of
the project? Does the applicant acknowledge potential problem areas and
consider alternative tactics?
INNOVATION: Does the project employ novel concepts, approaches or
methods? Are the aims original and innovative? Does the project
challenge existing paradigms or develop new methodologies or
technologies?
INVESTIGATOR: Is the investigator appropriately trained and well suited
to carry out this work? Is the work proposed appropriate to the
experience level of the principal investigator and other researchers
(if any)?
ENVIRONMENT: Does the scientific environment in which the work will be
done contribute to the probability of success? Do the proposed
experiments take advantage of unique features of the scientific
environment or employ useful collaborative arrangements? Is there
evidence of institutional support?
ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, all R21
applications will also be reviewed with respect to the following:
o In the context of this RFA, the R21 exploratory/developmental grants
are to be used to either: a) gather preliminary data to develop a
research basis for a subsequent application through other mechanisms,
i.e., R01, P01 or b) explore the feasibility of an innovative or
conceptually creative research question or approach that may not be
justifiable through existing research to compete as a standard research
project grant (e.g., R01).
o Preliminary data supporting feasibility of approach are not required.
PROTECTION OF HUMAN SUBJECTS FROM RESEARCH RISK: The involvement of
human subjects and protections from research risk relating to their
participation in the proposed research will be assessed. (See criteria
included in the section on Federal Citations, below).
INCLUSION OF WOMEN, MINORITIES AND CHILDREN IN RESEARCH: The adequacy
of plans to include subjects from both genders, all racial and ethnic
groups (and subgroups), and children as appropriate for the scientific
goals of the research. Plans for the recruitment and retention of
subjects will also be evaluated. (See Inclusion Criteria in the
sections on Federal Citations, below).
CARE AND USE OF VERTEBRATE ANIMALS IN RESEARCH: If vertebrate animals
are to be used in the project, the five items described under Section f
of the PHS 398 research grant application instructions (rev. 5/2001)
will be assessed.
BUDGET: The reasonableness of the proposed budget and the requested
period of support in relation to the proposed research.
RECEIPT AND REVIEW SCHEDULE
Letter of Intent Receipt Date: July 19, 2004
Application Receipt Date: August 19, 2004
Peer Review Date: TBA
Council Review: May, 2005
Earliest Anticipated Start Date: June 1, 2005
AWARD CRITERIA
Award criteria that will be used to make award decisions include:
o Scientific merit (as determined by peer review)
o Availability of funds
o Programmatic priorities.
REQUIRED FEDERAL CITATIONS
HUMAN SUBJECTS PROTECTION: Federal regulations (45CFR46) require that
applications and proposals involving human subjects must be evaluated
with reference to the risks to the subjects, the adequacy of protection
against these risks, the potential benefits of the research to the
subjects and others, and the importance of the knowledge gained or to
be gained.
http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm
DATA AND SAFETY MONITORING PLAN: Data and safety monitoring is required
for all types of clinical trials, including physiologic, toxicity, and
dose-finding studies (phase I); efficacy studies (phase II); efficacy,
effectiveness and comparative trials (phase III). The establishment of
data and safety monitoring boards (DSMBs) is required for multi-site
clinical trials involving interventions that entail potential risk to
the participants. (NIH Policy for Data and Safety Monitoring, NIH
Guide for Grants and Contracts, June 12, 1998:
http://grants.nih.gov/grants/guide/notice-files/not98-084.html).
INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH: It is the
policy of the NIH that women and members of minority groups and their
sub-populations must be included in all NIH-supported clinical research
projects unless a clear and compelling justification is provided
indicating that inclusion is inappropriate with respect to the health of
the subjects or the purpose of the research. This policy results from
the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43).
All investigators proposing clinical research should read the "NIH
Guidelines for Inclusion of Women and Minorities as Subjects in
Clinical Research - Amended, October, 2001," published in the NIH Guide
for Grants and Contracts on October 9, 2001
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html);
a complete copy of the updated Guidelines are available at
http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm.
The amended policy incorporates: the use of an NIH definition
of clinical research; updated racial and ethnic categories in
compliance with the new OMB standards; clarification of language
governing NIH-defined Phase III clinical trials consistent with the new
PHS Form 398; and updated roles and responsibilities of NIH staff and
the extramural community. The policy continues to require for all NIH-
defined Phase III clinical trials that: a) all applications or
proposals and/or protocols must provide a description of plans to
conduct analyses, as appropriate, to address differences by sex/gender
and/or racial/ethnic groups, including subgroups if applicable; and b)
investigators must report annual accrual and progress in conducting
analyses, as appropriate, by sex/gender and/or racial/ethnic group
differences.
INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN
SUBJECTS: The NIH maintains a policy that children (i.e., individuals
under the age of 21) must be included in all human subjects research,
conducted or supported by the NIH, unless there are scientific and
ethical reasons not to include them. This policy applies to all initial
(Type 1) applications submitted for receipt dates after October 1,
1998.
All investigators proposing research involving human subjects should
read the "NIH Policy and Guidelines" on the inclusion of children as
participants in research involving human subjects that is available at
http://grants.nih.gov/grants/funding/children/children.htm
REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS: NIH
policy requires education on the protection of human subject
participants for all investigators submitting NIH proposals for
research involving human subjects. You will find this policy
announcement in the NIH Guide for Grants and Contracts Announcement,
dated June 5, 2000, at
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.
HUMAN EMBRYONIC STEM CELLS (hESC): Criteria for federal funding of
research on hESCs can be found at http://stemcells.nih.gov/index.asp and
at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html.
Only research using hESC lines that are registered in the NIH Human
Embryonic Stem Cell Registry will be eligible for Federal funding (see
http://escr.nih.gov). It is the responsibility of the applicant to
provide, in the project description and elsewhere in the application as
appropriate, the official NIH identifier(s) for the hESC line(s)to be
used in the proposed research. Applications that do not provide this
information will be returned without review.
PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT:
The Office of Management and Budget (OMB) Circular A-110 has been
revised to provide public access to research data through the Freedom of
Information Act (FOIA) under some circumstances. Data that are (1)
first produced in a project that is supported in whole or in part with
Federal funds and (2) cited publicly and officially by a Federal agency
in support of an action that has the force and effect of law (i.e., a
regulation) may be accessed through FOIA. It is important for
applicants to understand the basic scope of this amendment. NIH has
provided guidance at
http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.
Applicants may wish to place data collected under this RFA in a public
archive, which can provide protections for the data and manage the
distribution for an indefinite period of time. If so, the application
should include a description of the archiving plan in the study design
and include information about this in the budget justification section
of the application. In addition, applicants should think about how to
structure informed consent statements and other human subjects
procedures given the potential for wider use of data collected under
this award.
STANDARDS FOR PRIVACY OF INDIVIDUALLY IDENTIFIABLE HEALTH INFORMATION:
The Department of Health and Human Services (DHHS) issued final
modification to the "Standards for Privacy of Individually Identifiable
Health Information", the "Privacy Rule," on August 14, 2002. The
Privacy Rule is a federal regulation under the Health Insurance
Portability and Accountability Act (HIPAA) of 1996 that governs the
protection of individually identifiable health information, and is
administered and enforced by the DHHS Office for Civil Rights (OCR).
Those who must comply with the Privacy Rule (classified under the Rule
as "covered entities") must do so by April 14, 2003 (with the
exception of small health plans which have an extra year to comply).
Decisions about applicability and implementation of the Privacy Rule
reside with the researcher and his/her institution. The OCR website
(http://www.hhs.gov/ocr/) provides information on the Privacy Rule,
including a complete Regulation Text and a set of decision tools on "Am
I a covered entity?" Information on the impact of the HIPAA Privacy
Rule on NIH processes involving the review, funding, and progress
monitoring of grants, cooperative agreements, and research contracts
can be found at
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.
URLs IN NIH GRANT APPLICATIONS OR APPENDICES: All applications and
proposals for NIH funding must be self-contained within specified page
limitations. Unless otherwise specified in an NIH solicitation, Internet
addresses (URLs) should not be used to provide information necessary to
the review because reviewers are under no obligation to view the
Internet sites. Furthermore, we caution reviewers that their anonymity
may be compromised when they directly access an Internet site.
HEALTHY PEOPLE 2010: The Public Health Service (PHS) is committed to
achieving the health promotion and disease prevention objectives of
"Healthy People 2010," a PHS-led national activity for setting priority
areas. This RFA is related to one or more of the priority areas.
Potential applicants may obtain a copy of "Healthy People 2010" at
http://www.health.gov/healthypeople.
AUTHORITY AND REGULATIONS: This program is described in the Catalog of
Federal Domestic Assistance at http://www.cfda.gov/ and is not subject
to the intergovernmental review requirements of Executive Order 12372
or Health Systems Agency review. Awards are made under the
authorization of Sections 301 and 405 of the Public Health Service Act
as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR 52
and 45 CFR Parts 74 and92. All awards are subject to the terms and
conditions, cost principles, and other considerations described in the
NIH Grants Policy Statement. The NIH Grants Policy Statement can be
found at http://grants.nih.gov/grants/policy/policy.htm.
The PHS strongly encourages all grant recipients to provide a smoke-
free workplace and discourage the use of all tobacco products. In
addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits
smoking in certain facilities (or in some cases, any portion of a
facility) in which regular or routine education, library, day care,
health care, or early childhood development services are provided to
children. This is consistent with the PHS mission to protect and
advance the physical and mental health of the American people.